Related Experiment Videos
Development of the lung in mice with bromodeoxyuridine-induced cleft palate
1Department of Anatomy, Faculty of Medicine, University College, Dublin, Ireland.
Insights
Bromodeoxyuridine (BUdR) exposure caused cleft palate and lung hypoplasia in mice. Cleft palate severely worsened lung development, impacting saccular volume but not cellular differentiation.
Area of Science:
- Developmental Biology
- Teratology
- Fetal Medicine
Background:
- Pulmonary hypoplasia is linked to restricted communication between amniotic and lung fluids.
- Cleft palate, potentially caused by tongue obstruction, may affect lung development.
- This association is observed in the human Pena-Shokeir phenotype.
Purpose of the Study:
- To investigate the impact of bromodeoxyuridine (BUdR)-induced cleft palate on fetal lung development in a mouse model.
- To determine if BUdR exposure alone or in conjunction with cleft palate affects lung growth and cellular differentiation.
Main Methods:
- LACA mice were administered BUdR during gestation (E11 or E11-E12).
- Incidence of cleft palate and lung development were assessed.
- Morphometric analysis and electron microscopy were used to evaluate lung structure and cell differentiation.
Main Results:
- BUdR exposure directly retarded lung growth.
- Fetal lungs with BUdR-induced cleft palate exhibited significantly reduced saccular volume compared to controls or BUdR-treated fetuses with normal palates.
- Despite hypoplasia, type I and type II pneumocytes were present, with type II cells demonstrating surfactant production capability.
Conclusions:
- BUdR-induced cleft palate exacerbates lung hypoplasia in mice.
- Cellular differentiation of lung tissue remains unaffected by BUdR treatment or cleft palate.
- This animal model partially mimics the lung abnormalities seen in the human Pena-Shokeir phenotype.
Abstract:
Clinical and laboratory observations show that denial of free communication between the amniotic fluid and lung fluid results in pulmonary hypoplasia. Thus, cleft palate resulting from tongue obstruction to palatal shelf elevation might be associated with disturbed lung development. This association exists in the Pena-Shokeir phenotype. The goal of these experiments was to see what effect bromodeoxyuridine (BUdR)-induced cleft palate had on lung development. LACA mice were injected with 500 mg/kg BUdR on E11 or E11 and E12 of gestation, a treatment known to produce a 25% and 50% incidence of cleft palate, respectively. BUdR had a direct retarding effect on lung growth but, when cleft palate occurred as well, the lungs were more severely affected. Morphometry showed that lungs from fetuses with cleft palate had only one-half the saccular volume of controls or of treated fetuses with normal palates. Although hypoplastic, lungs associated with cleft palate had type I and type II pneumocytes, and the latter were shown by electron microscopy to be capable of producing surfactant. Hence, cellular differentiation had not been affected by the treatment. Fetuses with cleft palate had less amniotic fluid than controls but significantly more than those with normal palates after treatment. Thus, the pattern of abnormalities in this animal model bears some resemblance to that of the human Pena-Shokeir phenotype.